Neural Activity Of Living Brains Captured Using Novel 3D Video

Researchers at MIT and the University of Vienna in Austria have devised an imaging method that shows neural action throughout the minds of living creatures. This technique, the very first that can create 3D videos of complete brains with the millisecond timescale, could help professionals understand how neuronal networks absorb sensory data and produce behavior, according to a new report published in the journal Nature Methods.

The team reported that they used the new system to simultaneously image the activity of every neuron in the worm Caenorhabditis elegans, and the entire brain of a zebrafish larva, offering a more complete picture of nervous system activity than has been previously possible.

“Looking at the activity of just one neuron in the brain doesn’t tell you how that information is being computed; for that, you need to know what upstream neurons are doing. And to understand what the activity of a given neuron means, you have to be able to see what downstream neurons are doing,” said study author Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT. “In short, if you want to understand how information is being integrated from sensation all the way to action, you have to see the entire brain.”

“We don’t really know, for any brain disorder, the exact set of cells involved,” Boyden added. “The ability to survey activity throughout a nervous system may help pinpoint the cells or networks that are involved with a brain disorder, leading to new ideas for therapies.”

The study team was able to create their novel imaging system by engineering fluorescent proteins to glow when they bind calcium, a crucial part of central nervous system functioning. The system scans the brain with a technology called light-field imaging, which creates 3-D images by calculating the angles of inbound rays of light. Microscopes that perform light-field imaging have been already developed by numerous groups – but in the new paper, the researchers enhanced the light-field microscope, and applied it to imaging neural activity.

With this type of microscope, the light released by the target is routed via a range of lenses that refracts the light in various directions. Every point of the sample produces about 400 different points of light, which can then be assembled into a three-dimensional image using a computer algorithm.

“If you have one light-emitting molecule in your sample, rather than just refocusing it into a single point on the camera the way regular microscopes do, these tiny lenses will project its light onto many points,” Boyden said. “From that, you can infer the three-dimensional position of where the molecule was.”

The study team said they used their novel system to capture neural activity in the worm C. elegans, the sole organism where the complete neural wiring diagram is known. This 1-millimeter worm has 302 neurons, every one of which the scientists imaged as the worm carried out normal behaviors. They also identified the neuronal reaction to sensory stimuli, such as smells.

While the current resolution is adequate for seeing the activity of particular neurons, the scientists are now focusing on enhancing it so the microscope could show smaller parts of neurons, such as the long dendrites that spread out from neurons’ principal structures. They are also focusing on accelerating the computing process, which presently takes a few minutes to evaluate one second of imaging information.